Quantifying the sediment sorption of organic ultraviolet filter chemicals using solvophobic theory.

Hydrophobic organic chemicals (HOCs) that enter the aquatic environment often negatively impact organisms, endangering aquatic biodiversity. Understanding sediment sorption equilibria for these chemicals can properly direct mitigation efforts. In addition, many HOCs of environmental concern lack sufficient environmental fate data to adequately assess their risk to ecosystems and humans. In this study, a sorption method addressing solvophobic effects was used to quantify the sorption of an HOC of current environmental concern, OD-PABA (padimate O, 2-ethylhexyl-4-(dimethylamino)benzoate), to a variety of sediments. OD-PABA is an organic ultraviolet filter chemical used in commercial sun protection products; it has been shown to exhibit cytotoxic effects and is known to photochemically transform under natural sunlight conditions. Given its commercial use, it enters the aquatic environment via recreational use and wastewater treatment plant effluent. OD-PABA is strongly hydrophobic; to mitigate the adsorption of OD-PABA to the container walls during sorption experiments, a precise concentration of methanol was used to avoid solvophobic effects. This sorption method was used to determine the sorption capacities for OD-PABA of four sediment samples, each with unique geochemical characteristics. Sediment-water distribution coefficients (Kd) were quantified and were normalized to various sediment characteristics to assess the main driving force(s) for sorption of OD-PABA. Organic carbon content was found to be a main driving force, with organic carbon-normalized distribution coefficients (log Koc) ranging from 4.4 - 4.6 for sediments with total organic carbon (TOC) > 10%); the clay fraction was also found to be important, especially for sediments with low TOC. The sorption of para-aminobenzoic acid (PABA), a water-soluble analog of OD-PABA was also investigated to assess the experimental approach, yielding a log Koc of 2.1 for the sediment with the greatest TOC.

Effect of Screening for Undiagnosed Atrial Fibrillation on Stroke Prevention.

BACKGROUND: Atrial fibrillation (AF) often remains undiagnosed, and it independently raises the risk of ischemic stroke, which is largely reversible by oral anticoagulation. Although randomized trials using longer term screening approaches increase identification of AF, no studies have established that AF screening lowers stroke rates. OBJECTIVES: To address this knowledge gap, the GUARD-AF (Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals) trial screened participants in primary care practices using a 14-day continuous electrocardiographic monitor to determine whether screening for AF coupled with physician/patient decision-making to use oral anticoagulation reduces stroke and provides a net clinical benefit compared with usual care. METHODS: GUARD-AF was a prospective, parallel-group, randomized controlled trial designed to test whether screening for AF in people aged ≥70 years using a 14-day single-lead continuous electrocardiographic patch monitor could identify patients with undiagnosed AF and reduce stroke. Participants were randomized 1:1 to screening or usual care. The primary efficacy and safety outcomes were hospitalization due to all-cause stroke and bleeding, respectively. Analyses used the intention-to-treat population. RESULTS: Enrollment began on December 17, 2019, and involved 149 primary care sites across the United States. The COVID-19 pandemic led to premature termination of enrollment, with 11,905 participants in the intention-to-treat population. Median follow-up was 15.3 months (Q1-Q3: 13.8-17.6 months). Median age was 75 years (Q1-Q3: 72-79 years), and 56.6% were female. The risk of stroke in the screening group was 0.7% vs 0.6% in the usual care group (HR: 1.10; 95% CI: 0.69-1.75). The risk of bleeding was 1.0% in the screening group vs 1.1% in the usual care group (HR: 0.87; 95% CI: 0.60-1.26). Diagnosis of AF was 5% in the screening group and 3.3% in the usual care group, and initiation of oral anticoagulation after randomization was 4.2% and 2.8%, respectively. CONCLUSIONS: In this trial, there was no evidence that screening for AF using a 14-day continuous electrocardiographic monitor in people ≥70 years of age seen in primary care practice reduces stroke hospitalizations. Event rates were low, however, and the trial did not enroll the planned sample size.(Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals [GUARD-AF]; NCT04126486).

Atrial Fibrillation Burden on a 14-Day ECG Monitor: Findings From the GUARD-AF Trial Screening Arm.

BACKGROUND: The "burden" of atrial fibrillation (AF) detected by screening likely influences stroke risk, but the distribution of burden is not well described. OBJECTIVES: This study aims to determine the frequency of AF and the distribution of AF burden found when screening individuals ≥70 years of age with a 14-day electrocardiograph monitor. METHODS: This is a cohort study of the screening arm of a randomized AF screening trial among those ≥70 years of age without a prior AF diagnosis (between 2019 and 2021). Screening was performed with a 14-day continuous electrocardiogram patch monitor. RESULTS: Analyzable patches were returned by 5,684 (95%) of screening arm participants; the median age was 75 years (Q1-Q3: 72-78 years), 57% were female, and the median CHA2DS2-VASc score was 3 (Q1-Q3: 2-4). AF was detected in 252 participants (4.4%); 29 (0.5%) patients had continuous AF and 223 (3.9%) had paroxysmal AF. Among those with paroxysmal AF, the average indices of AF burden were of low magnitude with right-skewed distributions. The median percent time in AF was 0.46% (Q1-Q3: 0.02%-2.48%), or 75 (Q1-Q3: 3-454) minutes, and the median longest episode was 38 (Q1-Q3: 2-245) minutes. The upper quartile threshold of 2.48% time in AF corresponded to 7.6 hours. Age greater than 80 years was associated with screen-detected AF in our multivariable model (OR: 1.46; 95% CI: 1.06-2.02). CONCLUSIONS: Most AF detected in these older patients was very low burden. However, one-quarter of those with AF had multiple hours of AF, raising concern about stroke risk. These findings have implications for targeting populations for AF screening trials and for responding to heart rhythm alerts from mobile devices (GUARD-AF [A Study to Determine if Identification of Undiagnosed Atrial Fibrillation in People at least 70 Years of Age Reduces the Risk of Stroke]; NCT04126486).

Assessing methods to ascertain persistence and adherence of oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: Persistence and adherence to oral anticoagulants (OACs) is crucial for its effectiveness in stroke prevention in atrial fibrillation (AF). We aimed to assess the impact of different ascertainment methods on estimated persistence rates. METHODS: We conducted a retrospective cohort study based on the Medicare claims data (01/01/2013-12/31/2019). We built an incident user cohort of OAC (apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) prescription filling. We measured OAC medication persistence and adherence using the following approaches: (1) treatment-anniversary based persistence: if there is an active prescription overlapping the 180th and 365th day with vs. without a 15-day buffer period (i.e., overlapping with 165th-195th and 350th-380th day); (2) dispensing-gap-based persistence: if there is OAC discontinuation defined as having gap between prescriptions more than a threshold (e.g., 5-60 days) and secondarily, (3) proportion of days covered (PDC) adherence: proportion of days in which patient had filled medication available over the 365-day interval. RESULTS: We identified 1,398,692 patients who initiated OACs during the study interval. With the treatment-anniversary based approach, only 51.2% to 65.4% of the patients persisted with the medication for either warfarin or DOACs at 180 days, and the number dropped to 43.4% to 60.7% at 1 year. Adding a 15-day buffer period increased the treatment-anniversary based persistence rates by 6.5% to 10.5%. When the allowable gap increased from 5 to 60 days, the persistence rates increased by 36.3% to 42.4% for all OACs. Apixaban users had the highest PDC (74%-75%) over the 365 days, compared to other OACs (60%-69%). CONCLUSIONS: We found that the estimated persistence rates are sensitive to the choice of ascertainment methods. When reporting and comparing persistence findings using the claims database, definitions of OAC discontinuation must be clearly delineated.

Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation : A Nationwide Cohort Study.

BACKGROUND: Apixaban, rivaroxaban, and warfarin have shown benefit for preventing major ischemic events, albeit with increased bleeding risk, among patients in the general population with atrial fibrillation (AF). However, data are scarce in patients with cirrhosis and AF. OBJECTIVE: To compare the effectiveness and safety of apixaban versus rivaroxaban and versus warfarin in patients with cirrhosis and AF. DESIGN: Population-based cohort study. SETTING: Two U.S. claims data sets (Medicare and Optum's de-identified Clinformatics Data Mart Database [2013 to 2022]). PARTICIPANTS: 1:1 propensity score (PS)-matched patients with cirrhosis and nonvalvular AF initiating use of apixaban, rivaroxaban, or warfarin. MEASUREMENTS: Primary outcomes included ischemic stroke or systemic embolism and major hemorrhage (intracranial hemorrhage or major gastrointestinal bleeding). Database-specific and pooled PS-matched rate differences (RDs) per 1000 person-years (PY) and Cox proportional hazard ratios (HRs) with 95% CIs were estimated, controlling for 104 preexposure covariates. RESULTS: Rivaroxaban initiators had significantly higher rates of major hemorrhagic events than apixaban initiators (RD, 33.1 per 1000 PY [95% CI, 12.9 to 53.2 per 1000 PY]; HR, 1.47 [CI, 1.11 to 1.94]) but no significant differences in rates of ischemic events or death. Consistently higher rates of major hemorrhage were found with rivaroxaban across subgroup and sensitivity analyses. Warfarin initiators also had significantly higher rates of major hemorrhage than apixaban initiators (RD, 26.1 per 1000 PY [CI, 6.8 to 45.3 per 1000 PY]; HR, 1.38 [CI, 1.03 to 1.84]), particularly hemorrhagic stroke (RD, 9.7 per 1000 PY [CI, 2.2 to 17.2 per 1000 PY]; HR, 2.85 [CI, 1.24 to 6.59]). LIMITATION: Nonrandomized treatment selection. CONCLUSION: Among patients with cirrhosis and nonvalvular AF, initiators of rivaroxaban versus apixaban had significantly higher rates of major hemorrhage and similar rates of ischemic events and death. Initiation of warfarin versus apixaban also contributed to significantly higher rates of major hemorrhagic events, including hemorrhagic stroke. PRIMARY FUNDING SOURCE: National Institutes of Health.

Identifying a Heterogeneous Effect of Atrial Fibrillation Screening in Older Adults: A Secondary Analysis of the VITAL-AF Trial.

Background: One-time atrial fibrillation (AF) screening trials have produced mixed results; however, it is unclear if there is a subset for whom screening is effective. Identifying such a subgroup would support targeted screening. Methods: We conducted a secondary analysis of VITAL-AF, a randomized trial of one-time, single-lead ECG screening during primary care visits. We tested two approaches to identify a subgroup where screening is effective. First, we developed an effect-based model using a T-learner. Specifically, we separately predicted the likelihood of AF diagnosis under screening and usual care conditions; the difference in probabilities was the predicted screening effect. Second, we used a validated AF risk model to test for a heterogeneous screening effect. We used interaction testing to determine if observed AF diagnosis rates in the screening and usual care groups differed when stratified by decile of the predicted screening effect and predicted AF risk. Results: Baseline characteristics were similar between the screening (n=15187) and usual care (n=15078) groups (mean age 74 years, 59% female). In the effect-based analysis, in the highest decile of predicted screening effectiveness (n=3026), AF diagnosis rates were higher in the screening group (6.50 vs. 3.06 per 100 person-years, rate difference 3.45, 95%CI 1.62 to 5.28). In this group, the mean age was 84 years and 68% were female. The risk-based analysis did not identify a subgroup where screening was more effective. Predicted screening effectiveness and predicted baseline AF risk were poorly correlated (Spearman coefficient 0.13). Conclusions: In a secondary analysis of the VITAL-AF trial, we identified a small subgroup where one-time screening was associated with increased AF diagnoses using an effect-based approach. In this study, predicted AF risk was a poor proxy for predicted screening effectiveness. These data caution against the assumption that high AF risk is necessarily correlated with high screening effectiveness.

Automated interpretations of single-lead electrocardiograms predict incident atrial fibrillation: The VITAL-AF trial.

BACKGROUND: Single-lead electrocardiograms (1L ECGs) are increasingly used for atrial fibrillation (AF) detection. Automated 1L ECG interpretation may have prognostic value for future AF in cases in which screening does not result in a short-term AF diagnosis. OBJECTIVE: We sought to investigate the association between automated 1L ECG interpretation and incident AF. METHODS: VITAL-AF was a randomized controlled trial investigating the effectiveness of screening for AF by 1L ECGs. For this study, participants were divided into 4 groups based on automated classification of 1L ECGs. Patients with prevalent AF were excluded. Associations between groups and incident AF were assessed by Cox proportional hazards models adjusted for risk factors. The start of follow-up was defined as 60 days after the latest 1L ECG (as some individuals had numerous screening 1L ECGs). RESULTS: The study sample included never screened (n = 16,306), normal (n = 10,914), other (n = 2675), and possible AF (n = 561). Possible AF had the highest AF incidence (5.91 per 100 person-years; 95% confidence interval [CI], 4.24-8.23). Possible AF was associated with greater hazard of incident AF compared with normal (adjusted hazard ratio, 2.48; 95% CI, 1.66-3.71). Other was associated with greater hazard of incident AF compared with normal (1.41; 95% CI, 1.04-1.90). CONCLUSION: In patients undergoing AF screening with 1L ECGs without prevalent AF or AF within 60 days of screening, presumptive positive and indeterminate 1L ECG interpretations were associated with future AF. Abnormal 1L ECG recordings may identify individuals at higher risk for future AF.

Assessment of Days Alive Out of Hospital as a Possible End Point in Trials of Stroke Prevention for Atrial Fibrillation: A ROCKET AF Analysis.

BACKGROUND: Days alive out of hospital (DAOH) is an objective and patient-centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. METHODS AND RESULTS: ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double-blind, double-dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator-reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (P=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, P=0.88). CONCLUSIONS: DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.

Development and Validation of an Intracranial Hemorrhage Risk Score in Older Adults with Atrial Fibrillation Treated with Oral Anticoagulant.

Background: High risk of intracranial hemorrhage (ICH) is a leading reason for withholding anticoagulation in patients with atrial fibrillation (AF). We aimed to develop a claims-based ICH risk prediction model in older adults with AF initiating oral anticoagulation (OAC). Methods: We used US Medicare claims data to identify new users of OAC aged ≥65 years with AF in 2010-2017. We used regularized Cox regression to select predictors of ICH. We compared our AF ICH risk score with the HAS-BLED bleed risk and Homer fall risk scores by area under the receiver operating characteristic curve (AUC) and assessed net reclassification improvement (NRI) when predicting 1-year risk of ICH. Results: Our study cohort comprised 840,020 patients (mean [SD] age 77.5 [7.4] years and female 52.2%) split geographically into training (3963 ICH events [0.6%] in 629,804 patients) and validation (1397 ICH events [0.7%] in 210,216 patients) sets. Our AF ICH risk score, including 50 predictors, had superior AUCs of 0.653 and 0.650 in the training and validation sets than the HAS-BLED score of 0.580 and 0.567 (p<0.001) and the Homer score of 0.624 and 0.623 (p<0.001). In the validation set, our AF ICH risk score reclassified 57.8%, 42.5%, and 43.9% of low, intermediate, and high-risk patients, respectively, by HAS-BLED score (NRI: 15.3%, p<0.001). Similarly, it reclassified 0.0, 44.1, and 19.4% of low, intermediate, and high-risk patients, respectively, by the Homer score (NRI: 21.9%, p<0.001). Conclusion: Our novel claims-based ICH risk prediction model outperformed the standard HAS-BLED score and can inform OAC prescribing decisions.

Estimating Vitamin K Antagonist Anticoagulation Benefit in People With Atrial Fibrillation Accounting for Competing Risks: Evidence From 12 Randomized Trials.

BACKGROUND: Patients with atrial fibrillation have a high mortality rate that is only partially attributable to vascular outcomes. The competing risk of death may affect the expected anticoagulant benefit. We determined if competing risks materially affect the guideline-endorsed estimate of anticoagulant benefit. METHODS: We conducted a secondary analysis of 12 randomized controlled trials that randomized patients with atrial fibrillation to vitamin K antagonists (VKAs) or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of VKAs to prevent stroke or systemic embolism using 2 methods-first using a guideline-endorsed model (CHA2DS2-VASc) and then again using a competing risk model that uses the same inputs as CHA2DS2-VASc but accounts for the competing risk of death and allows for nonlinear growth in benefit. We compared the absolute and relative differences in estimated benefit and whether the differences varied by life expectancy. RESULTS: A total of 7933 participants (median age, 73 years, 36% women) had a median life expectancy of 8 years (interquartile range, 6-12), determined by comorbidity-adjusted life tables and 43% were randomized to VKAs. The CHA2DS2-VASc model estimated a larger ARR than the competing risk model (median ARR at 3 years, 6.9% [interquartile range, 4.7%-10.0%] versus 5.2% [interquartile range, 3.5%-7.4%]; P<0.001). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA2DS2-VASc model - competing risk model 3-year risk) was -1.3% (95% CI, -1.3% to -1.2%); for those with life expectancies in the lowest decile, 3-year ARR difference was 4.7% (95% CI, 4.5%-5.0%). CONCLUSIONS: VKA anticoagulants were exceptionally effective at reducing stroke risk. However, VKA benefits were misestimated with CHA2DS2-VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced when life expectancy was low and when the benefit was estimated over a multiyear horizon.

Patient Characteristics Associated With Using Transcatheter Left Atrial Appendage Occlusion Versus Oral Anticoagulants for Atrial Fibrillation.

BACKGROUND: Transcatheter left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation, but the predictors of LAAO use in routine care are unclear. We aimed to assess the utilization trends of LAAO and compare the change in characteristics of LAAO users versus OACs since its marketing. METHODS: Using the US Medicare claims database (March 15, 2015, to December 31, 2020), we identified patients with atrial fibrillation, ≥65 years, and CHA2DS2-VASc score ≥2 (men) or ≥3 (women), with either first implantation of an LAAO device or initiation of OACs, including apixaban, dabigatran, rivaroxaban, edoxaban, or warfarin. Patient characteristics, measured 365 days before the first LAAO or OAC use date, were compared using logistic regression. RESULTS: There were 30 058 LAAO recipients (mean age, 77.74 years; female, 42.1%) and 792 600 OAC initiators (mean age, 78.48; female, 53.3%). In 2020, patients had higher odds of initiating LAAO use than in 2015 (0.52 versus 9.32%; adjusted odds ratio [aOR], 13.64 [95% CI, 12.56-14.81]). Old age (ie, >85 versus 65-75 years; aOR, 0.84 [95% CI, 0.80-0.88]), female sex (aOR, 0.74 [95% CI, 0.71-0.76]), Black race (aOR, 0.63 [95% CI, 0.58-0.68]) versus White race, and Medicaid eligibility (aOR, 0.61 [95% CI, 0.58-0.64]) were associated with lower odds of receiving LAAO. Among clinical characteristics, frailty, cancer, fractures, and venous thromboembolism were associated with lower odds of LAAO use, while history of intracranial and extracranial bleeding, coagulopathy, and falls were associated with higher odds of receiving LAAO. CONCLUSIONS: Among patients with atrial fibrillation receiving stroke-preventive therapy, LAAO use increased rapidly from 2015 to 2020 and was positively associated with the risk factors for OAC complications but negatively associated with old age, advanced frailty, and cancer. Black race and female sex were associated with a lower likelihood of receiving LAAO.

Predicting post-stroke cognitive impairment using electronic health record data.

BACKGROUND: Secondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification. AIMS: To develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records. METHODS: Cohort study that included primary care patients from two academic medical centers. Patients were aged 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003 and 2016 (development/internal validation cohort) or 2010 and 2022 (external validation cohort). Predictors of PSCI were ascertained from the electronic health record. The outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included. RESULTS: The analysis included 332 incident diagnoses of PSCI in the development cohort (n = 3741), and 161 and 128 incident diagnoses in the internal (n = 1925) and external (n = 2237) validation cohorts, respectively. The C-statistic for predicting PSCI was 0.731 (95% confidence interval (CI): 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-23 points) risk groups. The hazard ratios (HRs) for incident PSCI were significantly different by risk categories in internal (high, HR: 6.2, 95% CI: 4.1-9.3; Intermediate, HR: 2.7, 95% CI: 1.8-4.1) and external (high, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR: 2.8, 95% CI: 1.9-4.3) validation cohorts. CONCLUSION: Five-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts. DATA ACCESS STATEMENT: Mass General Brigham data contain protected health information and cannot be shared publicly. The data processing scripts used to perform analyses will be made available to interested researchers upon reasonable request to the corresponding author.

Brain MRI microbleeds and risk of intracranial hemorrhage in atrial fibrillation patients: A Swedish case-control study.

OBJECTIVES: Our goal was to quantify the independent association of brain microbleeds with future intracranial hemorrhage (ICrH). Microbleed findings on brain magnetic resonance imaging (MRI) may identify distinctive risk factors for ICrH which could inform the anticoagulant therapy decision for atrial fibrillation (AF) patients. Our study design includes patients with MRIs for numerous reasons, not limited to evaluation of stroke. MATERIALS AND METHODS: The source population was all patients with AF from a nationwide Swedish health care register. Case patients had an ICrH between 2006 and 2013 and ≥1 brain MRI for an unrelated condition before the ICrH. Each case was matched to four controls who had a brain MRI without a subsequent ICrH. The MRIs were re-reviewed by neuroradiologists. Associations between MRI findings and subsequent ICrH were assessed using logistic regression, adjusting for comorbidities and antithrombotic medications. RESULTS: A total of 78 cases and 312 matched controls were identified; 29 cases and 79 controls had MRI sequences suitable for analysis of microbleeds. Patients with ≥10 microbleeds had a markedly increased risk of ICrH (adjusted odds ratio 14.56; 95 % confidence interval: 2.86-74.16, p < 0.001). All patients with ≥10 microbleeds had microbleeds in the lobar region and ≥10 lobar microbleeds was associated with intracerebral hemorrhages, univariable OR 8.54 (2.01-36.33), p = 0.004. CONCLUSIONS: Leveraging a nationwide database with brain imaging obtained prior to ICrH, we identified a strong association between ≥10 microbleeds on brain MRI and subsequent ICrH among AF patients. Lobar brain regions were involved whenever there were ≥10 microbleeds. Brain MRIs may help optimize the anticoagulation decision in selected AF patients.

Predicting post-stroke cognitive impairment using electronic health record data.

Importance: Secondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification. Objective: To develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records. Design: Cohort study with patients enrolled between 2003-2016 with follow-up through 2022. Setting: Primary care practices affiliated with two academic medical centers. Participants: Individuals 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003-2016 (development/internal validation cohort) or 2010-2022 (external validation cohort). Exposures: Predictors of PSCI were ascertained from the electronic health record. Main Outcome: The outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using ICD-9/10 codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included. Results: The analysis included 332 incident diagnoses of PSCI in the development cohort (n=3,741), and 161 and 128 incident diagnoses in the internal (n=1,925) and external (n=2,237) validation cohorts. The c-statistic for predicting PSCI was 0.731 (95% CI: 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-35 points) risk groups. The hazard ratios for incident PSCI were significantly different by risk categories in internal (High, HR: 6.2, 95% CI 4.1-9.3; Intermediate, HR 2.7, 95% CI: 1.8-4.1) and external (High, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR 2.8, 95% CI: 1.9-4.3) validation cohorts. Conclusions and Relevance: Five-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts.

Identification of recurrent atrial fibrillation using natural language processing applied to electronic health records.

AIMS: This study aimed to develop and apply natural language processing (NLP) algorithms to identify recurrent atrial fibrillation (AF) episodes following rhythm control therapy initiation using electronic health records (EHRs). METHODS AND RESULTS: We included adults with new-onset AF who initiated rhythm control therapies (ablation, cardioversion, or antiarrhythmic medication) within two US integrated healthcare delivery systems. A code-based algorithm identified potential AF recurrence using diagnosis and procedure codes. An automated NLP algorithm was developed and validated to capture AF recurrence from electrocardiograms, cardiac monitor reports, and clinical notes. Compared with the reference standard cases confirmed by physicians' adjudication, the F-scores, sensitivity, and specificity were all above 0.90 for the NLP algorithms at both sites. We applied the NLP and code-based algorithms to patients with incident AF (n = 22 970) during the 12 months after initiating rhythm control therapy. Applying the NLP algorithms, the percentages of patients with AF recurrence for sites 1 and 2 were 60.7% and 69.9% (ablation), 64.5% and 73.7% (cardioversion), and 49.6% and 55.5% (antiarrhythmic medication), respectively. In comparison, the percentages of patients with code-identified AF recurrence for sites 1 and 2 were 20.2% and 23.7% for ablation, 25.6% and 28.4% for cardioversion, and 20.0% and 27.5% for antiarrhythmic medication, respectively. CONCLUSION: When compared with a code-based approach alone, this study's high-performing automated NLP method identified significantly more patients with recurrent AF. The NLP algorithms could enable efficient evaluation of treatment effectiveness of AF therapies in large populations and help develop tailored interventions.

Characteristics and Attitudes of Wearable Device Users and Nonusers in a Large Health Care System.

BACKGROUND: Consumer wearable devices with health and wellness features are increasingly common and may enhance disease detection and management. Yet studies informing relationships between wearable device use, attitudes toward device data, and comprehensive clinical profiles are lacking. METHODS AND RESULTS: WATCH-IT (Wearable Activity Tracking for Comprehensive Healthcare-Integrated Technology) studied adults receiving longitudinal primary or ambulatory cardiovascular care in the Mass General Brigham health care system from January 2010 to July 2021. Participants completed a 20-question electronic survey about perceptions and use of consumer wearable devices, with responses linked to electronic health records. Multivariable logistic regression was used to identify factors associated with device use. Among 214 992 individuals receiving longitudinal primary or cardiovascular care with an active electronic portal, 11 121 responded (5.2%). Most respondents (55.8%) currently used a wearable device, and most nonusers (95.3%) would use a wearable if provided at no cost. Although most users (70.2%) had not shared device data with their doctor previously, most believed it would be very (20.4%) or moderately (34.4%) important to share device-related health information with providers. In multivariable models, older age (odds ratio [OR], 0.80 per 10-year increase [95% CI, 0.77-0.82]), male sex (OR, 0.87 [95% CI, 0.80-0.95]), and heart failure (OR, 0.75 [95% CI, 0.63-0.89]) were associated with lower odds of wearable device use, whereas higher median income (OR, 1.08 per 1-quartile increase [95% CI, 1.04-1.12]) and care in a cardiovascular medicine clinic (OR, 1.17 [95% CI, 1.05-1.30]) were associated with greater odds of device use. CONCLUSIONS: Among patients in primary and cardiovascular medicine clinics, consumer wearable device use is common, and most users perceive value in wearable health data.

Frailty, Home Time, and Health Care Costs in Older Adults With Atrial Fibrillation Receiving Oral Anticoagulants.

Importance: There are no data on patient-centered outcomes and health care costs by frailty in patients with atrial fibrillation (AF) taking oral anticoagulants (OACs). Objective: To compare home time, clinical events, and health care costs associated with OACs by frailty levels in older adults with AF. Design, Setting, and Participants: This community-based cohort study assessed Medicare fee-for-service beneficiaries 65 years or older with AF from January 1, 2013, to December 31, 2019. Data analysis was performed from January to December 2022. Exposures: Apixaban, rivaroxaban, and warfarin use were measured from prescription claims. Frailty was measured using a validated claims-based frailty index. Main outcomes and measures: Outcome measures were (1) home time (days alive out of the hospital and skilled nursing facility) loss greater than 14 days; (2) a composite end point of ischemic stroke, systemic embolism, major bleeding, or death; and (3) total cost per member per year after propensity score overlap weighting. Results: The weighted population comprised 136 551 beneficiaries, including 45 950 taking apixaban (mean [SD] age, 77.6 [7.3] years; 51.3% female), 45 320 taking rivaroxaban (mean [SD] age, 77.6 [7.3] years; 51.9% female), and 45 281 taking warfarin (mean [SD] age, 77.6 [7.3] years; 52.0% female). Compared with apixaban, rivaroxaban was associated with increased risk of home time lost greater than 14 days (risk difference per 100 persons, 1.8 [95% CI, 1.5-2.1]), composite end point (rate difference per 1000 person-years, 21.3 [95% CI, 16.4-26.2]), and total cost (mean difference, $890 [95% CI, $652-$1127]), with greater differences among the beneficiaries with frailty. Use of warfarin relative to apixaban was associated with increased home time lost (risk difference per 100 persons, 3.2 [95% CI, 2.9-3.5]) and composite end point (rate difference per 1000 person-years, 29.4 [95% CI, 24.5-34.3]), with greater differences among the beneficiaries with frailty. Compared with apixaban, warfarin was associated with lower total cost (mean difference, -$1166 [95% CI, -$1396 to -$937]) but higher cost when excluding OAC cost (mean difference, $1409 [95% CI, $1177 to $1642]) regardless of frailty levels. Conclusions and Relevance: In older adults with AF, apixaban was associated with increased home time and lower rates of clinical events than rivaroxaban and warfarin, especially for those with frailty. Apixaban was associated with lower total cost compared with rivaroxaban but higher cost compared with warfarin due to higher OAC cost. These findings suggest that apixaban may be preferred for older adults with AF, particularly those with frailty.